Baicalin potentiates cefquinome against animal-origin ESBL-Escherichia coli by attenuating resistance-associated phenotypes and intestinal injury.

Animal-origin extended-spectrum β-lactamase-producing Escherichia coli (ESBL-E. coli) undermines cefquinome (CEF) efficacy in veterinary medicine, necessitating strategies that enhance antibacterial activity while protecting intestinal integrity. Here, we evaluated baicalin (BAI), a flavonoid from Scutellaria baicalensis, as a CEF adjuvant against animal-origin ESBL-E. coli. In a mouse intestinal infection model, BAI combined with CEF significantly improved survival, mitigated intestinal pathology, and downregulated Tlr4, Myd88, and NF-κB signaling. The combination preserved mucosal architecture and partially restored intestinal microbiota composition. In vitro, BAI potentiated CEF activity by suppressing blaCTX-M gene expression, reducing ESBL-mediated CEF hydrolysis, and limiting the emergence of reduced CEF susceptibility during serial passage. Docking suggested a potential interaction of BAI with the catalytic site of CTX-M-9; together with reduced cefquinome hydrolysis in whole-cell suspensions, this suggests interference with ESBL-mediated hydrolysis. These results demonstrate that BAI functions as a CEF sensitizer, integrating pathogen-directed and host-protective effects, and offer a translationally relevant strategy for veterinary antibiotic adjuvant therapy.